The most common cancer of the blood is lymphoma, but that designation encompasses a wide range of illnesses. The genetic underpinnings of the disease are not well understood, and this murky understanding and highly variable presentation make treating it very challenging. Researchers at the Duke Cancer Institute have been trying to learn more about the genetic basis of the most prevalent type, diffuse large B cell lymphoma, and how genes impact a patient’s response to treatment.
Reporting in Cell, the investigators assessed tumors taken from 1,001 patients that were affected by diffuse large B cell lymphoma in the past decade. These patients had gotten treatment at twelve different institutions that were located around the world. Learn more about the work from the video.
A type of genetic analysis that looks selectively at genes that have been expressed as proteins, whole exome sequencing, was utilized to identify genetic drivers of lymphoma. They found 150, many of which are newly revealed. The researchers next investigated whether any correlation could be found between the genes they identified, and how well patients had responded to various therapeutics.
The researchers also used the gene-editing tool called CRISPR and individually eliminated each of the 20,000 genes in lymphoma cells. They wanted to know which of these genes was essential for lymphoma growth.
After combing the results they had obtained from the various methods, several new and important genetic links were uncovered. The scientists are hopeful that their new work can now be applied to patient therapeutics and will improve treatment success.
"This work provides a comprehensive roadmap in terms of research and clinical priorities," said Sandeep Davé, M.D., a Professor of Medicine at Duke. "We have very good data now to pursue new and existing therapies that might target the genetic mutations we identified. Additionally, this data could also be used to develop genetic markers that steer patients to therapies that would be most effective."
Diffuse B cell lymphoma is described as “an aggressive type of non-Hodgkin lymphoma that develops from the B-cells in the lymphatic system” by the Leukemia Foundation. It usually presents as non-painful swelling around the lymph nodes, although other areas of the body are sometimes affected as well. It can impact a person at any age but usually occurs after the age of 50, and is a little more common in men than in women. The causes are unknown, and because of the aggressive nature of the illness, it must be treated quickly for the best possible outcome. It is fatal if untreated, but roughly two-thirds of patients who receive treatment will survive.